Posters
Presenting Author Academic/Professional Position
Abdel Martinez Borrego, MD
Academic Level (Author 1)
Resident
Discipline/Specialty (Author 1)
Internal Medicine
Academic Level (Author 2)
Resident
Discipline/Specialty (Author 2)
Internal Medicine
Academic Level (Author 3)
Faculty
Discipline/Specialty (Author 3)
Internal Medicine
Discipline Track
Clinical Science
Abstract Type
Case Report
Abstract
Background: Persistent fever in neutropenic patients with acute myeloid leukemia (AML) often raises concern for invasive fungal infections (IFIs), especially when unresponsive to broad-spectrum antibiotics and first-line antifungal agents like voriconazole. Invasive aspergillosis (IA), primarily caused by Aspergillus fumigatus, is a major cause of morbidity and mortality in this population, with mortality rates exceeding 50% in refractory cases. The emergence of azole-resistant Aspergillus, now reported in up to 10–15% of isolates in some regions, has complicated management. Patients may present with nonspecific symptoms such as persistent fevers, as well as concerning findings like cutaneous lesions—a clue to hematogenous spread—and multiple pulmonary nodules on imaging, suggestive of angioinvasive disease. In such cases, timely recognition of possible voriconazole resistance is essential to guide escalation of antifungal therapy and improve outcomes.
Case presentation: A 90-year-old patient with a past medical history of acute myeloid leukemia (AML) was admitted to the hospital with neutropenic fever and cellulitis of the left second digit. On admission, the absolute neutrophil count (ANC) was 0.0. The patient was started on broad-spectrum antibiotics with meropenem. Antifungal coverage with micafungin and antiviral therapy with acyclovir were also initiated. Despite treatment, the patient remained febrile for several days. During hospitalization, he required multiple transfusions due to pancytopenia secondary to AML and ongoing chemotherapy.
Physical examination revealed nodular, papular, and necrotic skin lesions that progressed over the course of admission. Imaging of the affected hand—including ultrasound, X-ray, and CT scan—showed moderate degenerative changes and joint space narrowing, but no evidence of abscess, osteomyelitis, or erosive lesions. Chest X-ray was unremarkable. Blood, urine, and MRSA cultures were negative, as were respiratory and gastrointestinal pathogen panels. Transthoracic echocardiogram showed a left ventricular ejection fraction of 50–55%, without evidence of vegetations.
Due to persistent fever after four days, further imaging was obtained. CT of the chest revealed approximately 17 new small pulmonary nodules not seen on previous imaging. CT of the sinuses showed partial opacification of the right frontal and ethmoid sinuses. Voriconazole was initiated, and infectious disease was consulted. Serum galactomannan antigen returned positive, raising concern for invasive aspergillosis. Given the progressive necrotic skin lesions and multiple lung nodules, there was high clinical suspicion for disseminated invasive fungal infection, with differentials including aspergillosis, mucormycosis, scedosporium, and fusarium.
Unfortunately, the patient respectfully declined treatment with amphotericin B due to concerns about renal toxicity and also declined a skin biopsy.
Conclusions: This case highlights the importance of adhering to established clinical algorithms in the evaluation and management of febrile neutropenia. According to the UpToDate-recommended algorithm, patients with persistent fever after 4–7 days of broad-spectrum antibiotics and ongoing neutropenia should undergo further evaluation for invasive fungal infections, including chest CT and empiric initiation of antifungal therapy, typically with an echinocandin or a mold-active azole such as voriconazole. In this patient, persistent fever for nearly 12 days, progressive necrotic skin lesions, and newly identified pulmonary nodules raised strong concern for disseminated invasive fungal infection. Although voriconazole was started appropriately, the limited clinical response and severity of presentation warranted consideration of escalation to amphotericin B, particularly in cases of suspected resistant or non-Aspergillus molds such as mucormycosis or fusarium. However, treatment was declined by the patient due to concerns regarding renal toxicity, and biopsy confirmation was not obtained. This case underscores the diagnostic and therapeutic challenges in immunocompromised hosts and the need for timely, aggressive workup and intervention when managing refractory neutropenic fever.
Presentation Type
Poster
Recommended Citation
Martinez Borrego, Abdel; Bhatti, Sahir; and Gutierrez, Cesar, "Refractory Neutropenic Fevers in AML: Unmasking Voriconazole-Resistant Invasive Aspergillosis" (2025). Research Colloquium. 1.
https://scholarworks.utrgv.edu/colloquium/2025/posters/1
Included in
Refractory Neutropenic Fevers in AML: Unmasking Voriconazole-Resistant Invasive Aspergillosis
Background: Persistent fever in neutropenic patients with acute myeloid leukemia (AML) often raises concern for invasive fungal infections (IFIs), especially when unresponsive to broad-spectrum antibiotics and first-line antifungal agents like voriconazole. Invasive aspergillosis (IA), primarily caused by Aspergillus fumigatus, is a major cause of morbidity and mortality in this population, with mortality rates exceeding 50% in refractory cases. The emergence of azole-resistant Aspergillus, now reported in up to 10–15% of isolates in some regions, has complicated management. Patients may present with nonspecific symptoms such as persistent fevers, as well as concerning findings like cutaneous lesions—a clue to hematogenous spread—and multiple pulmonary nodules on imaging, suggestive of angioinvasive disease. In such cases, timely recognition of possible voriconazole resistance is essential to guide escalation of antifungal therapy and improve outcomes.
Case presentation: A 90-year-old patient with a past medical history of acute myeloid leukemia (AML) was admitted to the hospital with neutropenic fever and cellulitis of the left second digit. On admission, the absolute neutrophil count (ANC) was 0.0. The patient was started on broad-spectrum antibiotics with meropenem. Antifungal coverage with micafungin and antiviral therapy with acyclovir were also initiated. Despite treatment, the patient remained febrile for several days. During hospitalization, he required multiple transfusions due to pancytopenia secondary to AML and ongoing chemotherapy.
Physical examination revealed nodular, papular, and necrotic skin lesions that progressed over the course of admission. Imaging of the affected hand—including ultrasound, X-ray, and CT scan—showed moderate degenerative changes and joint space narrowing, but no evidence of abscess, osteomyelitis, or erosive lesions. Chest X-ray was unremarkable. Blood, urine, and MRSA cultures were negative, as were respiratory and gastrointestinal pathogen panels. Transthoracic echocardiogram showed a left ventricular ejection fraction of 50–55%, without evidence of vegetations.
Due to persistent fever after four days, further imaging was obtained. CT of the chest revealed approximately 17 new small pulmonary nodules not seen on previous imaging. CT of the sinuses showed partial opacification of the right frontal and ethmoid sinuses. Voriconazole was initiated, and infectious disease was consulted. Serum galactomannan antigen returned positive, raising concern for invasive aspergillosis. Given the progressive necrotic skin lesions and multiple lung nodules, there was high clinical suspicion for disseminated invasive fungal infection, with differentials including aspergillosis, mucormycosis, scedosporium, and fusarium.
Unfortunately, the patient respectfully declined treatment with amphotericin B due to concerns about renal toxicity and also declined a skin biopsy.
Conclusions: This case highlights the importance of adhering to established clinical algorithms in the evaluation and management of febrile neutropenia. According to the UpToDate-recommended algorithm, patients with persistent fever after 4–7 days of broad-spectrum antibiotics and ongoing neutropenia should undergo further evaluation for invasive fungal infections, including chest CT and empiric initiation of antifungal therapy, typically with an echinocandin or a mold-active azole such as voriconazole. In this patient, persistent fever for nearly 12 days, progressive necrotic skin lesions, and newly identified pulmonary nodules raised strong concern for disseminated invasive fungal infection. Although voriconazole was started appropriately, the limited clinical response and severity of presentation warranted consideration of escalation to amphotericin B, particularly in cases of suspected resistant or non-Aspergillus molds such as mucormycosis or fusarium. However, treatment was declined by the patient due to concerns regarding renal toxicity, and biopsy confirmation was not obtained. This case underscores the diagnostic and therapeutic challenges in immunocompromised hosts and the need for timely, aggressive workup and intervention when managing refractory neutropenic fever.
